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Deuteration has emerged as a significant method for investigating kinetic isotope effects in chemical reactions. In recent years, research on deuteration has revealed that this reaction often alters the pharmacokinetic or toxicological properties of drug molecules, thereby enhancing their therapeutic effect. Therefore, deuteration is considered as a potential avenue for drug research direction. Since the approval of the first deuterated drug, "deutetrabenazine," by the American Food and Drug Administration (FDA) in 2017, deuteration has been applied in the development of a variety of novel drugs. Research on deuteration technology has matured with the publication of numerous deuteration strategies. This article reviews recently reported strategies for late‐stage selective deuteration, discusses the challenges associated with current deuteration strategies, and presents future prospects for the synthesis of deuterated drugs. [ABSTRACT FROM AUTHOR]

Objective: To detect brain alterations in intensive care unit (ICU) patients who develop delirium using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) and to determine their predictive value. Methods: Fifty-two patients who were admitted to the ICU of the Affiliated Hospital of Zunyi Medical University between June 2021 and June 2022 were enrolled. Fifteen patients who were diagnosed with delirium by the Intensive Care Delirium Screening Checklist (ICDSC) after MRI were selected as the delirium group, and 15 healthy volunteers who were examined during the same period served as the control group. Both groups underwent fMRI and DTI. Quantitative fMRI and DTI data were compared between the two groups to detect abnormal structural and functional brain damage. The relationships between MRI outliers and clinical indicators in the delirium group were also assessed. Results: Demographic characteristics and imaging indicators before delirium were not correlated with ICDSC scores after delirium. Compared with the healthy control group, the delirium group had significantly lower regional homogeneity (ReHo) values in the left caudate nucleus and frontal lobe on fMRI. The amplitude of the low-frequency fluctuations (ALFF) values of the delirium group were significantly increased in the hippocampus but significantly decreased in the frontal lobe. Compared with the healthy control group, the delirium group showed reduced mean diffusivity (MD) values, mainly in the right cerebellum and right middle temporal gyrus; reduced radial diffusivity (RD) values, mainly in the anterior cerebellum and right middle temporal gyrus; reduced fractional anisotropy (FA) values, only in the corpus callosum; and reduced axial diffusivity (AD) values, mainly in the anterior cerebellar lobe, right middle temporal gyrus, and left middle frontal gyrus on DTI. The statistical thresholds for quantitative DTI measurements were p < 0.005 at the voxel level and a cluster size > 5. Conclusion: Abnormal resting-state brain activity in the left superior frontal gyrus and structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus, and cerebellum were observed in ICU patients who developed delirium during hospitalization. Early-brain fMRI and DTI examinations are recommended for the prediction of delirium according to unique quantitative indicators to facilitate early intervention for critically ill patients, reduce the length of hospital stay, and improve patient prognosis. [ABSTRACT FROM AUTHOR]

1,4-dioxane is a potential carcinogen in water and is difficult to deal with due to its robust cycloether bond and complete miscibility with water. To remove 1,4-dioxane in an economically viable and environmentally friendly way, a series of carbon aerogels were synthesized as adsorbents for 1,4-dioxane. The experiment results showed that adsorption performances were closely related to the preparation conditions of carbon aerogels, such as the molar ratio, heating rate, pyrolysis temperature and residence time, which were carefully controlled. Scanning electron microscope analysis revealed the presence of a three-dimensional porous network structure in carbon aerogels. Brunauer–Emmett–Teller analysis results demonstrated an increase in specific surface area (673.89 m2/g) and total pore volume after carbonization, with an increase in mesoporous porosity and a decrease in microporosity. When considering each variable individually, the highest specific surface area of prepared carbon aerogels was achieved at a pyrolysis temperature of 800 °C, a holding time of 1 h, and a heating rate of 2 °C/min. Under optimal experimental conditions, the adsorption removal of 1,4-dioxane by carbon aerogels exceeded 95%, following quasi-second-order kinetics and Langmuir isothermal adsorption isotherms, indicating that monolayer adsorption on the surface of carbon aerogels occurred. The maximum adsorption capacity obtained was 67.28 mg/g at a temperature of 318 K, which was attributed to the presence of a large proportion of mesopores and abundant micropores simultaneously in carbon aerogels. Furthermore, with the interference of chlorinated solvents such as trichloroethylene (TCE), the removal efficiency of 1,4-dioxane had no obvious inhibition effect. Regeneration experiments showed that after five continuous cycles, the carbon aerogels still kept a comparable adsorption capacity, which illustrates its potential application in 1,4-dioxane-polluted water purification. [ABSTRACT FROM AUTHOR]

We have disclosed an alkenes dicarbofunctionalization method to introduce alkyl and electron‐rich aryl across the C=C bond of styrenes under copper catalyst and oxidative conditions, leading to construct C(sp3)‐C(sp2)/C(sp3)‐C(sp3) bonds via dual C−H functionalization. This method realizes the synthesis of 1,1‐diarylalkanes, which are very important skeleton in natural products and drug molecules, through the grafting of electron‐rich aromatics, including indoles, pyrroles, trisubstituted aromatic. [ABSTRACT FROM AUTHOR]

We have developed a new radical-mediated alkoxypolyhaloalkylation of styrenes with polychloroalkanes and alcohols for the facile synthesis of complex polyhaloalkanes. 4-Methoxybenzenediazonium tetrafluoroborate is a good radical initiator for this transformation. This protocol is well applied to the late-stage functionalization of complex molecules, including vitamin E, estrone and cholesterol derivatives. [ABSTRACT FROM AUTHOR]

Owing to their easy availability and cheapness, simple alkyl chlorides are good raw materials for introducing complex polychlorinated groups. Polychlorinated hydrocarbons units, such as di‐ or trichloromethyl groups, not only widely found in pesticide and bioactive molecule, but also can be as a precursor to converted into different functional groups such as −COOH, −CHO and −CO. The direct polychloroalkylation reaction by using simple alkyl chlrides has been considered to be an important tool for synthesizing complex polychlorinated compounds. This review summarizes recent developments, especially free radical strategies, in the polychloroalkylation of different substrates (such as 2‐acylpyridines, benzyl tertiary amines, alkenes, imine and 1,n‐enynes). We hope that this review provides a new perspective on this field and also provides a reference to develop environmentally friendly and sustainable methods. [ABSTRACT FROM AUTHOR]

The γ-lactone skeleton is very important component of various natural products, biological molecules, food additives, and perfumes. As a result, much effort has been made towards such compounds. In this review, we summarize recent progress in transition-metal-catalyzed annulation reactions for the formation of γ-lactone derivatives through a radical pathway. Various reagents, such as anhydrides, Togni's reagent, TMSN3 , arenesulfonyl chlorides, arenediazonium salts, dibenzoyl peroxides, O -benzoylhydroxylamine, NFSI, and α-halocarboxylic compounds, used in radical cyclization reactions are described, and the mechanisms of these radical annulation reactions are also discussed. 1 Introduction 2 Annulations of Alkenes with Anhydrides 3 Annulations of Unsaturated Carboxylic Acids with Nucleophiles 4 Annulations of Alkenes with α-Halocarboxylic Compounds 5 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

We have developed a new oxidative decarboxylation of cinnamic acids with 4-alkyl-1,4-dihydropyridines to construct C(sp3)–C(sp2) bonds in the presence of copper catalyst and dicumyl peroxide (DCP). A variety of internal alkenes have been obtained with mild conditions, broad substrate scope and excellent functional group tolerance. This method has significant potential for application by using inexpensive and stable cinnamic acids instead of alkenyl halides and nitro-olefins. [ABSTRACT FROM AUTHOR]

Radical‐initiated difunctionalization of alkenes is one of the most important methods in organic synthesis and medicinal chemistry, which can be applied to synthesize value complex compounds as well as structural motifs that found in bioactive natural products and pharmaceuticals. In recent years, impressive progress have been made in this area with ideal silver catalysis. Here, we summarize recent advances in silver‐mediated radical difunctionalization of alkenes for the formation of diverse bonds, including 1) two‐component radical difunctionalization reactions enabled by an intramolecular cyclization process toward various cyclic compounds and 2) three‐component radical difunctionalization reactions leading to complex linear compounds. These silver‐mediated radical alkene difunctionalization transformations are general initiated by different radicals, such as carbon‐, oxygen‐, sulfur‐, phosphinyl‐, and halogen‐center radicals, followed by terminated with nucleophiles to form two new bonds in a single reaction. [ABSTRACT FROM AUTHOR]

A copper and silver‐promoted intermolecular 1,2‐alkylarylation of styrenes with α‐carbonyl alkyl bromides and arenes for producing highly bulky 1,1‐diarylalkane derivatives has been developed. In this transformations, two new C−C bonds were formed in a single reaction step through C−Br bond cleavage and C(sp2)−H functionalization. This protocol tolerates a variety of α‐carbonyl alkyl bromides, including primary, secondary and tertiary α‐bromoalkyl ketone esters. [ABSTRACT FROM AUTHOR]

A new external oxidant-free electrochemical dehydrogenative cross-coupling of xanthenes and ketones for the preparation of functionalized 9-alkyl-9H-xanthenes was developed. This method enables the formation of a new C(sp3)–C(sp3) bond through release of H2 as the major byproduct at room temperature, and features mild conditions, high atom economy, excellent functional-group tolerance, scalability and facile applications in pharmaceutical chemistry. [ABSTRACT FROM AUTHOR]

Traditional fine-grained image recognition is required to distinguish different subordinate categories (e.g., birds species) based on the visual cues beneath raw images. Due to both small inter-class variations and large intra-class variations, it is desirable to capture the subtle differences between these sub-categories, which is crucial but challenging for fine-grained recognition. Recently, language modality aggregation has been proved as a successful technique to improve visual recognition in the experience. In this paper, we introduce an end-to-end trainable Progressive Mask Attention (PMA) model for fine-grained recognition by leveraging both visual and language modalities. Our Bi-Modal PMA model can not only stage-by-stage capture the most discriminative part in the visual modality by our mask-based fashion, but also explore the out-of-visual-domain knowledge from the language modality in an interactional alignment paradigm. Specifically, at each stage, a self-attention module is proposed to attend to the key patch from images or text descriptions. Besides, a query-relational module is designed to seize the key words/phrases of texts and further bridge the connection between two modalities. Later, the learned representations of bi-modality from multiple stages are aggregated as the final features for recognition. Our Bi-Modal PMA model only needs raw images and raw text descriptions, without requiring bounding boxes/part annotations in images or key word annotations in texts. By conducting comprehensive experiments on fine-grained benchmark datasets, we demonstrate that the proposed method achieves superior performance over the competing baselines, on either vision and language bi-modality or single visual modality. [ABSTRACT FROM AUTHOR]

We here describe a new, selective indium-promoted silver-mediated intermolecular oxidative 1,4-alkylarylation of 1,3-dienes with α-carbonyl alkyl bromides and N-heterocycles for producing functionalized N-heterocycles, which is characterized by its exquisitely controllable regio-/stereo-selectivity and excellent tolerance of functional groups. Mechanistically, the formation of the carbonyl-coordinated η3-allyl-In complex radical intermediate is the key factor for successfully achieving regio- and stereo-selectivity toward 1,4-difunctionalization and (E)-isomers. [ABSTRACT FROM AUTHOR]

The In(OTf)3-promoted three-component photoredox alkylarylation of styrenes with alkyl NHP esters and arenes to access alkylated arene derivatives through C–C bond cleavage and C–H functionalization is reported. By utilizing visible-light photoredox catalysis, alkyl N-hydroxyphthalimide esters serving as alkyl carbon-centered radicals and a wide range of arenes (e.g., indoles, pyrrole, and electron-rich arenes) as nucleophiles were used to enable the introduction of various alkyl groups and aryl groups across the C＝C bonds with excellent selectivity and functional group tolerance. [ABSTRACT FROM AUTHOR]

Novel adsorbent, diethylenetriamine-grafted Spirodela polyrhiza (DSP), was synthesized via modifying natural S. polyrhiza (SP) with diethylenetriamine by cross-linking with epichlorohydrin and applied to adsorb Ni2+ and Pb2+ from water. The effecting parameters on adsorption of Ni2+ and Pb2+ such as adsorbent dosage, pH, contact time, temperature, and initial concentration were studied through equilibrium experiments. The adsorption of Ni2+ and Pb2+ followed the pseudo-second-order model and the Langmuir isotherm adsorption model. The study discusses thermodynamic parameters, including changes in Gibbs free energy, entropy, and enthalpy, for the adsorption of Ni2+ and Pb2+ on DSP, and revealed that the adsorption process was spontaneous and exothermic under natural conditions. The maximum Ni2+ and Pb2+ adsorption capacities of DSP were 33.02 and 36.50 mg/g, respectively. The newly prepared materials were characterized through scanning electron microscopy (SEM), mapping analysis, and zeta potential analysis. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses indicated that functional groups (-OH and N-H) were involved in Ni2+ and Pb2+ adsorption. Notably, DSP can be easily regenerated and reused for multiple cycles. Therefore, DSP is a promising adsorbent for effective Ni2+ and Pb2+ removal. [ABSTRACT FROM AUTHOR]

A new, general silver-catalyzed oxidative 1,2-alkyletherification of unactivated olefinic ketones with primary, secondary and tertiary α-bromoalkyl carbonyls promoted by tert-butyl hydroperoxide (TBHP) and Et3N has been developed. Through the cooperative action of Ag2O, TBHP and Et3N, the reaction enables the construction of highly valuable quaternary-carbon-possessing 2,3-dihydrofuran frameworks using a concomitant intramolecular annulation strategy. [ABSTRACT FROM AUTHOR]

A new, practical directed anodic C–H sulfonylation of N,N-disubstituted anilines with sodium sulfinates for producing o- or p-amino arylsulfones and diarylsulfones is described. Employing the anodic strategy, the reaction proceeds efficiently under mild (room temperature) and transition-metal- and chemical oxidant-free conditions, and enables the formation of C–S bonds via directed activation of ortho- or para-C–H bond to the amino group with broad substrate scope and excellent site selectivity. [ABSTRACT FROM AUTHOR]

A highly para-selective amination of anilines with phenothiazines for producing various functionalized 10-aryl-10H-phenothiazines is reported. The oxidative amination reaction proceeds electrochemically at room temperature, thereby avoiding the use of metals and oxidizing reagents with excellent functional group tolerance and broad substrate scope. [ABSTRACT FROM AUTHOR]

A new copper-catalyzed three-component oxidative 1,2-trifluoromethylarylation of styrenes with NaSO2CF3 and indoles involving aryl C–H bond functionalization is described. This reaction is initiated by single electron transfer upon utilizing TBPB as an oxidant, thus enabling introduction of a CF3 group and an aryl group into the C=C bond of alkenes in a single step. This method represents a highly atom and step-economical access to various CF3-substituted 1,1-diarylalkane derivatives in moderate to good yields with good functional group compatibility. [ABSTRACT FROM AUTHOR]

Functionalization of alkenes has been well investigated by chemists, thus it has been extensively applied in organic synthesis and industries. In the past few decades, transition‐metal, such as palladium, rhodium, gold, iridium, copper and iron, catalyzed functionalization reactions of alkenes have been significantly developed and played vital roles in synthesis. The difunctionalization of alkenes are appealing as an important alternative to the traditional approaches for the construction of useful carbon centers, particularly carbon quaternary centers, which commonly existed as structural motifs in numerous natural products, pharmaceuticals, and biologically active molecules. This account will summarize our recent advances in the intermolecular difunctionalization of alkenes, and also highlight the scope and limitations as well as the mechanisms of these difunctionalization reactions. In general, in this account the difunctionalization of alkenes starting from dicarbofunctionalization will be discussed. Then carboheterofunctionalization of alkenes will be intensively reviewed, and diheterofunctionalization will also be highlighted. This personal account introduces the recent advances in difunctionalization of alkenes. These reactions are classified by the chemical bond formation, including C−C, C−N, C−O and other carbon‐heteroatom bond formation. This review highlights the scope and limitations, as well as the mechanisms of these functionalization reactions. [ABSTRACT FROM AUTHOR]

A new ruthenium(ii)-catalyzed electrooxidative [4+2] annulation of primary benzylic alcohols with internal alkynes is described, which enables benzylic alcohols as weakly directing group precursors to access isocoumarins via multiple C–H functionalization. The reaction works well with a broad substrate scope, tolerates a wide range of functional groups, and incorporates practically the isocoumarin unit into diverse bioactive molecules. Mechanistic studies indicate that activation of aryl C(sp2)–H bonds is achieved through the generation of the active benzoyloxy–Ru(ii) intermediates via oxidation of benzylic alcohols using an electrooxidative Ru(ii) catalyst. [ABSTRACT FROM AUTHOR]

A new copper-catalyzed oxidative three-component intermolecular 1,2-alkylarylation of styrenes with ethers and indoles is disclosed. This method utilizes TBPB as an oxidant to efficiently construct C(sp3)–C(sp3) and C(sp3)–C(sp2) bonds in one step through probable radical and electrophilic alkylation processes, respectively, and a variety of functional groups are well tolerated. [ABSTRACT FROM AUTHOR]

For straightforward access to various substituted 1,1-diarylalkanes a photoredox-catalyzed and copper-promoted 1,2-alkylarylation reaction of styrenes has been developed, which uses α-carbonyl alkyl bromides and N,N-disubstituted anilines as functionalization reagents. In this radical difunctionalization reaction, α-carbonyl alkyl bromides, including primary-, secondary- and tertiary-α-bromoalkyl ketone esters, malonic esters and cycloalkane were transformed to the corresponding 1,1-diarylalkanes in moderate to good yields at room temperature. Notably, this transformation provided a new route for the C–H alkylation of N,N-disubstituted anilines with high para-selectivity beyond the typical Friedel–Crafts alkylation. [ABSTRACT FROM AUTHOR]

An indium-promoted intermolecular oxidative 1,2-alkylarylation of alkenes with alkyl nitriles and N-heteroarenes enabled by C(sp3)–H/C(sp2)–H functionalization is presented. This oxidative radical strategy allows the formation of two new C–C bonds through transformations of two different C–H bonds across the alkenes in a controlled single-step manner, and offers a general, highly atom-economic route for the production of new functionalized N-heteroarenes, including indoles, pyrrolo[2,3-b]pyridine, pyrrolo[3,2,1-ij]quinolone and pyrroles. [ABSTRACT FROM AUTHOR]

Abstract: A new palladium‐catalyzed reductive [5+1] cycloaddition of 3‐acetoxy‐1,4‐enynes with CO, enabled by hydrosilanes, has been developed for delivering valuable functionalized phenols. This methodology employs hydrosilanes as the external reagent to facilitate the [5+1] carbonylative benzannulation. The reaction is a conceptually and mechanistically novel carbonylative cycloaddition route for the construction of substituted phenols, through the formation of four new chemical bonds, with excellent functional‐group tolerance. [ABSTRACT FROM AUTHOR]

Abstract: α‐Carbonyl alkyl bromides are powerful reactive species for the formation of carbon–carbon bonds. Strategies relying on intermolecular C−H functionalization and cross‐coupling reactions, also referred to as intramolecular cyclization, have been employed for the construction of alkenes, alkanes, ketones, and other natural‐product‐like ring compounds from simple alkynes, alkenes, and 1,n‐enynes. In view of the importance of these α‐carbonyl alkyl bromides, especially the difluoro carbonyl alkyl bromides, many researchers have focused their efforts to develop facile and mild synthetic methods for compounds with important biological activities. This review aims to briefly discuss the latest developments in the transformation of α‐carbonyl alkyl bromides with emphasis on the related reaction mechanisms. [ABSTRACT FROM AUTHOR]

A copper-catalyzed oxidative radical strategy to avoid the use of the highly expensive noble metal/ligand catalytic systems is described, which allows selective activation of dual chemical bonds around the Si-atom center relying on the nature of alkylsilanes. While for tertiary silanes selective functionalization of Si–H/silyl C(sp3)–H bonds in intermolecular oxidative annulation cascades with N-(2-(ethynyl)aryl)acrylamides toward silino[3,4-c]quinolin-5(3H)-ones, when using secondary silanes and HSi(TMS)3, dual Si–H bonds or Si–H/Si–Si bonds are selectively cleaved leading to 4H-silolo[3,4-c]quinolin-4-ones. [ABSTRACT FROM AUTHOR]

A Mn-promoted intermolecular oxidative radical heteroannulation of N-(2-cyanoaryl)-acrylamides and tertiary silanes has been described, which provides an efficient route to produce silicon/nitrogen heterocycles, sila-analogues of the known carbon-based structural motifs prevalent in bioactive natural products, pharmaceuticals and materials. The reaction enables Si-incorporation by controlling accurately several chemical bond cleavage and formation processes. Moreover, this reaction represents a new one-step construction of 1,3-azasiline-fused quinolinones that was achieved via silyl C(sp3)–H functionalization using an oxidative radical strategy. [ABSTRACT FROM AUTHOR]

A new metal-free oxidative cascade methylation/cyclization of benzene-linked 1,7-enynes to construct methylated polyheterocyclic scaffold skeletons is described. In this transformation, three new C-C bonds and two new rings are formed. Notably, di- tert-butyl peroxide (DTBP) acts not only as a radical initiator but also as an efficient methyl source. [ABSTRACT FROM AUTHOR]

A new palladium-catalyzed dearomatizative [2 + 2 + 1] carboannulation of 1,7-enynes with aryl diazonium salts and H2O is presented. The reaction enables the construction of spirocyclohexadienone-fused cyclopenta[c]quinolin-4(5H)-ones through a sequence of Heck-type addition, 6-exo-dig cyclization, ipso-cyclization, dearomatization and hydrolysis. [ABSTRACT FROM AUTHOR]

The first iron-catalyzed 1,2-difunctionalization of styrenes and conjugated alkenes with silanes and either N or C, using an oxidative radical strategy, is described. Employing FeCl2 and di- tert-butyl peroxide allows divergent alkene 1,2-difunctionalizations, including 1,2-aminosilylation, 1,2-arylsilylation, and 1,2-alkylsilylation, which rely on a wide range of nucleophiles, namely, amines, amides, indoles, pyrroles, and 1,3-dicarbonyls, thus providing a powerful platform for producing diverse silicon-containing alkanes. [ABSTRACT FROM AUTHOR]

A new divergent intermolecular cascade annulation reaction of N-(arylsulfonyl)acrylamides with dual alkyl C(sp3)–H bonds for producing two types of five-membered rings, indanes and pyrrolidin-2-ones, is described. By using cycloalkanes and common alkanes as a one-carbon unit, an intermolecular [4+1] cascade carboannulation of N-(arylsulfonyl)acrylamides was achieved via a sequence of three C–H bond functionalization/aryl migration/desulfonylation that enables the formation of three C–C bonds and one N–H bond. When the one-carbon unit was changed to cycloalkyl ethers, the alternative intermolecular [4+1] cascade heteroannulation reaction occurred and allowed the construction of two C–C bonds and one C–N bond through dual C–H bond functionalization, aryl migration and desulfonylation cascades. [ABSTRACT FROM AUTHOR]

A new route to producing 3-alkyl spiro[4,5]trienones via nickel-promoted radical oxidative ipso-annulation of N-( p-methoxyaryl)propiolamides with α-carbonyl alkyl bromides using TBHP oxidant is described. The method allows the formation of three new C-C bonds through a sequence of oxidative C-Br bond cleavage, ipso-cyclization and dearomatization, and represents a new alkyne 1,2-difunctionalization to access to the construction of spiro[4,5]trienones. [ABSTRACT FROM AUTHOR]

A novel copper-promoted [2+2+2] annulation of 1,n-enynes with azobis(alkyl nitrile)s and H2O for the synthesis of diverse 7,8-dihydrophenanthridine-6,9(5H,6aH)-diones and fluorene is described. The reaction proceeds via the decomposition of azobis(alkyl nitrile)s into the cyanoalkyl radicals as the two-carbon units and offers a new efficient tool for the one-step formation of four new chemical bonds. [ABSTRACT FROM AUTHOR]